Pre-mild Cognitive Impairment Research Articles

The overall and domain-specific quality of life of Chinese community-dwelling older adults: the role of intrinsic capacity and disease burden.

This study aimed to investigate the impact of the different domains of intrinsic capacity (IC) and chronic disease burden on health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults. A cross-sectional observational study of a community-based cohort. We evaluated Chinese older adults (n = 429, mean age, 72.91 ± 7.014 years; female proportion, 57.30%). IC contains five domains, namely locomotion, vitality, cognition, psychological, and sensory capacity. Locomotion dysfunction was defined as grip and/or gait decline. Vitality decline was defined if two of the following three parameters were present: fatigue, physical inactivity, and weight loss or overweight. Cognition was classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative z-scores of the neuropsychological test battery. Psychological dysfunction was diagnosed based on depressive symptoms. Sensory dysfunction was defined as hearing and/or vision impairment. HRQoL was assessed using the AQoL-8D scale, which comprised physical (including independent living, senses, and pain) and psychosocial (including mental health, happiness, self-worth, coping, and relationships) dimensions. Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychological confounders. Sensory impairment was an independent determinant of senses, and locomotion impairment was significantly associated with overall HRQoL, independent living, and pain in the physical dimension of HRQoL. Cognition was an independent determinant of the senses. Vitality was independently associated with overall HRQoL, senses, and pain in the physical dimension and mental health and relationships in the psychological dimension of HRQoL. The psychological domain of IC was independently associated with overall and domain-specific HRQoL apart from senses after adjustment for all confounders. The number of multimorbidities mainly had a significant impact on independent living after adjustment for all confounders. IC domains and chronic disease burden had heterogeneous influences on overall and domain-specific HRQoL. The impairment of sensory and locomotion domains had a synergistic impact on the overall and physical dimensions of HRQoL. The vitality and psychological domains of IC had more profound effects on HRQoL. Older people with high morbidity might have a higher risk of poor independent living.

The Cognitive Stress Test (CST): An Innovative Tool to Differentiate Cognitively Unimpaired (CU) Older Adults from those with Pre‐Mild Cognitive Impairment (Pre‐MCI) and Amnestic MCI (aMCI).

AbstractBackgroundThe CST is a novel assessment that was designed to measure cognitive changes during preclinical and prodromal stages of AD, that include aMCI and PreMCI, where deficits do not meet MCI. The CST employs semantically competing word lists to measure the impact of semantic interference, failure to recover from proactive semantic interference (frPSI), and its persistent effects, despite multiple trials. We hypothesized that frPSI deficits on the CST would be persistent in pre‐MCI and aMCI groups when compared to cognitively unimpaired (CU) controls.Method50 aMCI, 31 pre‐MCI, and 69 CU elders were administered the CST. Participants were presented with List A (18 semantically related words: occupations, household items, or transportation methods) for three initial learning trials, followed by three learning trials of List B, a categorically similar wordlist, to examine PSI and frPSI. Retroactive Semantic Interference (RSI) was assessed by using category cues to elicit recall of List A targets, followed by an additional learning trial to examine failure to recover from RSI (frRSI).ResultSignificant differences were observed between all diagnostic groups across CST Cued Recall trials that measure maximum learning, PSI, frPSI, and persistent frPSI. PreMCI and aMCI participants experienced deficits in learning List B despite two additional opportunities; a deficit that was observed even after adjusting for initial learning strength. Older adults with greater risk (preMCI and aMCI) performed similarly on indices that measures PSI, frPSI, and persistent frPSI as compared to controls. There were differences in RSI among CU and aMCI groups yet measuring frRSI did not differentiate groups. aMCI participants made more semantic intrusion errors on recall trials that cued List B words. Pre‐MCI and CU made a similar number of intrusion errors.ConclusionThe CST extends our work by assessing persistent effects of frPSI, which have been shown to predict neurodegenerative progression and have been associated with multiple biomarkers of AD. The finding that persistent frPSI could differentiate CU from preMCI groups is a promising indicator that semantic interference deficits persist in older adults that present a heightened risk for progression to dementia and is worthy of further research.

The Effect of Daily Practice of Puzzle-Game Apps on Cognition in Two Groups of Older Adults: A Pre-Post Experimental Study.

There is an urgent need for non-pharmacological cognitive interventions to delay the onset and modify the progression of the cognitive deterioration of older adults with early stages of cognitive decline. 'Tablet Enhancement of Cognition and Health' (TECH) is such an intervention. We aimed to assess the suitability of TECH for older adults with and without mild cognitive impairment (MCI). Specifically, we wanted to explore the feasibility and to determine the initial effectiveness of TECH for older adults with Pre-Mild Cognitive Impairment (pre-MCI) as well as with MCI. This is pre-post experimental design, including two groups of older adults. Feasibility included group session attendance (adherence), self-training time (compliance), and satisfaction from the TECH intervention. The Montreal Cognitive Assessment (MoCA) assessed global cognition and the WebNeuro computerized battery assessed specific cognitive components. Twenty-eight participants with MCI (8 women, aged 65-87), and ten participants with pre-MCI (5 women, aged 65-86) participated in TECH. High adherence, compliance, and satisfaction were reported by both groups. Memory recall improved for the MCI group (z = -2.7 p = 0.006). In addition, for the MoCA an intermediate effect size (Cohen's d = 0.52) and a small effect (Cohen's d = 0.18) were found for the MCI and pre-MCI groups, respectively. Large to small effect size values for WebNeuro cognitive components were found for both groups. Both groups of older adults were motivated, performed daily self-training, which gave them enjoyment and a sense of control. TECH seems to have potential to preserve cognition over time. Additional research with a longer follow-up is needed to determine whether TECH can prevent cognitive decline in older adults with MCI but especially with pre-MCI.

Development of the Story Telling Examination for Early Mild Cognitive Impairment (Pre-Mild Cognitive Impairment) Screening

Introduction: Cognitive function prior to mild cognitive impairment (MCI) has become a burgeoning interest. Tools used to detect this early period before MCI are being pilot-tested. This study aimed to develop a new test to detect pre-MCI and to examine its content validity and feasibility. Methods: The Story Telling Examination for Early MCI Screening (STEEMS), an audio cognitive test, was developed. It covers ten cognitive domains, e.g., executive function, language fluency, abstract reasoning. Face and content validity were examined by experts in geriatric psychiatry and psychology. The content validity index was 1.00. STEEMS comprised 12 items with 2–4 types of scoring. The tool was further examined in 16 pilot samples for feasibility among healthy participants having no cognitive impairment (Montreal Cognitive Assessment [MoCA] test score ≥25, Mini-Cog ≥3) and no depressive symptoms (Geriatric Depression Scale <6). Results: The 16 healthy older individuals aged 59–73 years, mean age was 65.06 ± 4.07 years, were predominantly males (68.8%). STEEMS scores ranged from 10 to 25, with a mean of 18.38 (SD = 4.2). Thirteen percent obtained 100% correct on the STEEMS, 63% scored 68–92% correct, and 25% scored 40–60% correct. The pre-MCI scores are illustrated by a bell curve’s graphical depiction, suggesting a normal distribution probability distribution. Correlation between STEEMS and MoCA test scores was observed. STEEMS showed to be feasible for early elderly or late adults as being brief and easy to understand. The time spent to administer was predictably less than 7 min. Discussion/Conclusion: STEEMS could potentially serve as a tool for pre-MCI screening. Further study and investigation in a larger population are required.

Neuropsychological, Metabolic, and Connectivity Underpinnings of Semantic Interference Deficits Using the LASSI-L.

LASSI-L is a novel neuropsychological test specifically designed for the early diagnosis of Alzheimer's disease (AD) based on semantic interference. To examine the cognitive and neural underpinnings of the failure to recover from proactive semantic and retroactive semantic interference. One hundred and fifty-five patients consulting for memory loss were included. Patients underwent neuropsychological assessment, including the LASSI-L, and FDG-PET imaging. They were categorized as subjective memory complaints (SMC) (n=32), pre-mild cognitive impairment (MCI) due to AD (Pre-MCI) (n=39), MCI due to AD (MCI-AD) (n=71), and MCI without evidence of neurodegeneration (MCI-NN) (n=13). Voxel-based brain mapping and metabolic network connectivity analyses were conducted. A significant group effect was found for all the LASSI-L scores. LASSI-L scores measuring failure to recover from proactive semantic interference and retroactive semantic interference were predicted by other neuropsychological tests with a precision of 64.1 and 44.8%. The LASSI-L scores were associated with brain metabolism in the bilateral precuneus, superior, middle and inferior temporal gyri, fusiform, angular, superior and inferior parietal lobule, superior, middle and inferior occipital gyri, lingual gyrus, and posterior cingulate. Connectivity analysis revealed a decrease of node degree and centrality in posterior cingulate in patients showing frPSI. Episodic memory dysfunction and the involvement of the medial temporal lobe, precuneus and posterior cingulate constitute the basis of the failure to recover from proactive semantic interference and retroactive semantic interference. These findings support the role of the LASSI-L in the detection, monitoring and outcome prediction during the early stages of AD.

Persistent Failure to Recover from Proactive Semantic Interference on the Cognitive Stress Test Differentiates Between Amnestic Mild Cognitive Impairment, Pre-Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults.

Susceptibility to proactive semantic interference (PSI) and the inability to ameliorate these difficulties with one additional learning trial have repeatedly been implicated as early features of incipient Alzheimer's disease (AD). Unfortunately, persistent failure to recover from PSI (frPSI) after repeated learning trials, are not captured by existing memory measures, or been examined in pre-mild cognitive impairment (PreMCI). A novel Cognitive Stress Test (CST) was employed to measure the impact of PSI, initial failure to recover from PSI and persistent effects of PSI, despite multiple learning trials of the new to-be-remembered material (pfrPSI). We hypothesized that PSI deficits on the CST would persist in both PreMCI and amnestic MCI (aMCI) groups over repeated learning trials when compared to cognitively unimpaired (CU) older adults. One hundred fifty older adults (69 CU, 31 PreMCI, and 50 aMCI) underwent a standardized clinical and neuropsychological evaluation. The CST was independent of diagnostic classification. Even after adjusting for strength of initial learning, aMCI and PreMCI groups demonstrated greater persistent PSI (pfrPSI) relative to the CU group despite repeated learning trials of List B. Further, the aMCI group made a higher number of semantic intrusion errors relative to the PreMCI and CU groups on all List B Cued Recall trials. Persistent PSI appears to be a common feature of aMCI and PreMCI. The possible theoretical mechanisms and empirical implications of these new findings are discussed.

Pre-dementia cognitive impairment

Cognitive disorders are one of the most significant problems of older. Special attention should be paid to the diagnosis of early pre-dementia stages of cognitive impairment (CI): subjective, subtle and mild.The aim of this study was to determine the criteria of pre-mild: subjective and subtle cognitive decline (SCD).Material and methods. The study included 602 patients with pre-mild cognitive impairment with a mean age of 63.24±11.24 years and 515 patients with mild cognitive impairment aged 71.2±8.0 years. The indicators of patients were compared with those of 104 healthy people (average age 64.23±8.14 years) who did not complain of memory impairment and had no deviations during clinical and neuropsychological examination.Results and discussion. Groups of patients with subjective and subtle cognitive decline were distinguished, which differed in most characteristics. At the same time, in both groups of patients, deviations in the results of neuropsychological tests did not exceed one standard deviation from the average results for healthy people, which, in fact, allowed them to be attributed to «pre-mild» cognitive decline. The data obtained confirmed the heterogeneity of the «pre-mild» cognitive decline. The study also shows the allocation limitation of pre-mild cognitive impairment only on the basis of a formal approach based on the quantitative characteristics of neuropsychological research with a difference from control groups necessarily exceeding one standard deviation.Conclusion. The analysis showed the heterogeneity of pre-dementia and pre-mild cognitive impairments that are divided according to the degree of changes in objectively assessed cognitive functions with the similarity of subjective complaints. It is proposed to distinguish subjective cognitive decline with completely normal neuropsychological characteristics and subtle cognitive decline in the event of changes in individual indicators evaluating mainly the control functions and memory.

Hippocampus-Based Dynamic Functional Connectivity Mapping in the Early Stages of Alzheimer's Disease.

The hippocampus with varying degrees of atrophy was a crucial neuroimaging feature resulting in the declining memory and cognitive function in Alzheimer's disease (AD). However, the abnormal dynamic functional connectivity (DFC) in both white matter (WM) and gray matter (GM) from the left and right hippocampus remains unclear. To explore the abnormal DFC within WM and GM from the left and right hippocampus across the different stages of AD. Current study employed the OASIS-3 dataset including 43 mild cognitive impairment (MCI), 71 pre-mild cognitive impairment (pre-MCI), and matched 87 normal cognitive (NC). Adopting the FMRIB's Integrated Registration and Segmentation Tool, we obtained the left and right hippocampus mask. Based on above hippocampus mask as seed point, we calculated the DFC between left/right hippocampus and all voxel time series within whole brain. One-way ANOVA analysis was performed to estimate the abnormal DFC among MCI, pre-MCI, and NC groups. We found that MCI and pre-MCI groups showed the common abnormalities of DFC in the Temporal_Mid_L, Cingulum_Mid_L, and Thalamus_L. Specific abnormalities were found in the Cerebelum_9_L and Precuneus of MCI group and Vermis_8 and Caudate_L of pre-MCI group. In addition, we found that DFC within WM regions also showed the common low DFC for the Cerebellum anterior lobe-WM, Corpus callosum, and Frontal lobe-WM in MCI and pre-MCI group. Our findings provided a novel information for discover the pathophysiological mechanisms of AD and indicate WM lesions were also an important cause of cognitive decline in AD.

Cognitive decline related to substance consumption in a Colombian kindred with familial Alzheimer's disease: A retrospective cohort study

AbstractBackgroundSubstance use is a presumed risk factor for Alzheimer's Disease (AD). So, it would be essential to evaluate it in people who already have a high risk of dementia. Neuroscience Group of Antioquia, GNA, is a research group from Medellin, Colombia, which studies Presenilin 1 (PS1) E280A mutation carriers. These carriers will course four stages of AD: 1) asymptomatic Pre‐Mild Cognitive Impairment (Pre‐MCI), 2) symptomatic pre‐MCI, 3) MCI; and 4) Dementia. Substance consumption could modify age‐at‐onset of those stages, but this association has not been deeply explored.MethodWe performed a retrospective cohort study with 163 subjects enrolled between January 25, 2019, and April 29, 2020. Of those participants, 69 (42.3%) were non‐carriers, and 94 (57.7%) were carriers. A psychiatrist interviewed the subjects through the "CACoS" questionnaire, an instrument specifically designed for this research. The subjects' cognitive information included CERAD test battery, MMSE, CDR, and a subjective memory complaints checklist. We analyzed the relationship between the onset of AD stages and substance consumption through a time‐to‐event analysis (survival analysis and Cox proportional hazards regression).ResultFor dementia onset, there was an association with less than one time per month of alcohol consumption in the last year (HR 0.42, CI 0.18‐0.96). For MCI onset, there was a relationship with less than one time per month of alcohol consumption in the last year (HR 0.39, CI 0.17‐0.91), and also with consumption of 5 to 11 drinks per day of consumption in the previous twelve months (HR 0.12, CI 0.01‐0.99). For pre‐MCI onset, there was a relationship with daily coffee consumption throughout life (HR 2.37, CI 1.07‐5.25).ConclusionA low frequency of alcohol consumption could be protective against MCI and dementia, but coffee was associated with Pre‐MCI acceleration. It would be critical to continue exploring these substances' role as modifiable risk factors soon.

Brain metabolism, amyloid load and neuropsychological correlates in preclinical dementia stages

This multicenter study aimed to investigate the presence of early cognitive, behavioural and brain changes in individuals with subjective cognitive decline (SCD) and pre-Mild Cognitive Impairment (pre-MCI).

Manifestation of cognitive impairments after a prior coronavirus infection COVID-19 in a patient with ApoE ε4 genotype

Nowadays, the novel coronavirus infection (COVID-19) pandemic is one of the most important global health problems. There is increasing evidence that COVID-19 affects central and peripheral nervous system as well. The paper presents a clinical case of a 47 old patient with the ApoE ε4 haplotype and family history of Alzheimer’s disease who developed cognitive impairment after acute COVID-19. Before the infection the patient has no cognitive complaints and preserved everyday activity. After novel coronavirus infection, which was observed in mild form, the patient had started to complain on constant excessive forgetfulness. Neuropsychological assessment confirmed the presence of pre-mild cognitive impairment of predominantly single domain amnestic type. However, brain MRI showed only subtle periventricular white matter changes usually attributed to small vessel disease. Memory complaints were observed for 3 months of follow up despite intensive cognitive training, optimization of lifestyle and therapy with choline alphoscerate. Probable links between coronavirus infectious and cognitive impairment manifestation are discussed. There is data that ApoE ε4 haplotype is associated with increase of microglia mediated neuro-inflammation and it can be significant for accelerating of progression of neurodegenerative diseases after COVID-19. Further follow up of the patient is necessary for determination of nosological diagnosis explaining manifested predominantly amnestic type pre-mild cognitive impairment.

Clinical and Objective Cognitive Measures for the Diagnosis of Cognitive Frailty Subtypes: A Comparative Study.

BackgroundCognitive frailty (CF) includes reversible and potentially reversible subtypes; the former is known as concurrent physical frailty (PF) and pre-mild cognitive impairment subjective cognitive decline (pre-MCI SCD), whereas the latter is known as concurrent PF and MCI. The diagnoses of pre-MCI SCD and MCI are based on clinical criteria and various subjective cognitive decline questionnaires. Heterogeneous assessment of cognitive impairment (CI) results in significant variability of CI, CF, and their subtype prevalence in various population-based studies.ObjectiveThis study aimed to compare the classification differences in CI and CF subtypes from PF and normal cognition by applying clinical and objective cognitive criteria. Clinical criteria comprised Fried PF and clinical MCI criteria combined with the SCD questionnaire, whereas objective criteria comprised Fried PF and objective cognitive criteria based on the norm-adjusted six neuropsychological test scores.MethodsOf the 335 volunteers (age ≥ 60 years) in this study, 191 were diagnosed with CI based on clinical cognitive diagnosis criteria, and 144 were identified as robust normal based on objective cognitive assessment from the community-dwelling older adult cohort. Individuals with clinical CI, including 94 with MCI and 97 with pre-MCI SCD, were reclassified into different z-score-derived MCI, pre-MCI SCD, and normal subgroups based on objective cognitive criteria. The classification diagnostic accuracy of normal cognition, PF, pre-MCI, MCI, CF, and CF subtypes based on clinical and objective criteria was compared before and after adjusting for age, sex, and education level.ResultsThe reclassification of objective assessments indicated better performance than that of clinical assessments in terms of discerning CI severity among different subgroups before adjusting for demographic factors. After covariate adjustment, clinical assessments significantly improved the ability to cognitively discriminate normal individuals from those with pre-MCI SCD and MCI but not the z-score-derived pre-MCI SCD and MCI groups from the robust normal group. Furthermore, the adjustment did not improve the ability to discriminate among individuals with reversible CF from those with potentially reversible CF and pre-MCI only SCD from MCI only SCD.ConclusionsObjective criteria showed better performance than clinical criteria in the diagnosis of individuals with CI or CF subtypes. Rapid clinical cognitive screening in combination with normative z-scores criteria is cost effective and sustainable in clinical practice.

Demographically Corrected Normative Z Scores on the Neuropsychological Test Battery in Cognitively Normal Older Chinese Adults

Background: Subjective questionnaires used for the diagnosis of pre-mild cognitive impairment (pre-MCI) and conventional criteria for MCI might mainly result in false-positive diagnostic errors. The integrated criteria based on demographically adjusted total and process Z scores on neuropsychological tests have been validated to be sensitive for measuring pre-MCI, MCI, and MCI subtypes. However, the underrepresentativity of Chinese populations and the complexity in some tests limit the use of the established Z scores in the elderly Chinese population. Objective: The aim of this study was to develop a useful Z score calculator to assess individual cognitive performance after adjustment of the scores on each of the neuropsychological tests according to sex, age, and education and to establish preliminary norms for the objective assessment of cognition function in elderly Chinese individuals. Methods: The neuropsychological test battery consists of measures of performance on different cognitive domains, including episodic memory, language, executive function, processing speed, and attention. Data were obtained from 220 clinically cognitively normal Chinese volunteers aged 60 years or older from the cohort of the Shanghai study of health promotion among frail elderly individuals. Regression models were used to investigate the impact of age, education, and sex on test scores. Z scores were estimated for the different scores by subtracting the predicted mean from the raw score and dividing it by the root mean square error term for any given linear regression model. Results: Preliminary analyses indicated that age, sex, or level of education significantly affected test scores. A series of linear regression models was constructed for all instruments, i.e.: the Trail-Making Test A and B, to assess executive function or attention; the Boston Naming Test and animal list generation, to assess language; delayed free correct responses and the Hopkins Verbal Learning Test-Revised (HVLT-R) recognition, as well as three process scores, i.e., intrusion errors, learning slope, and retroactive interference, from the HVLT-R, to assess memory, by adjusting for the covariates of age, sex, and level of education concurrently. The Z scores on all neuropsychological tests were estimated based on the corresponding regression coefficients. Conclusions: We constructed a multivariable regression-based normative Z score method for the measurement of cognition among older Chinese individuals in the community. The normative score will be useful for the accurate diagnosis of different subtypes of pre-MCI and MCI after preliminary rapid screening in the community.

A-01 Objective and Subjective Cognitive Declines as Complementary Symptoms of Early Alzheimer’s Disease

Abstract Objective Subjective and objective cognitive declines are given equal weight as symptoms of pre-mild cognitive impairment in Alzheimer’s disease by recent research criteria. However, the overlap of these constructs is unclear. We used standardized regression-based (SRB) change to define subtle objective cognitive decline across serial neuropsychological assessments. We then examined the associations between objective change and subjective cognitive complaints. Finally, we investigated the impact of different symptom combinations on rates of classification for the early stages of the Alzheimer’s Continuum. Method Data from 1,341 cognitively intact older adults with serial Uniform Data Set 3.0 Neuropsychological Battery assessments (6–24-month follow-ups) were used to compute SRB declines at the following z-scores cut-points: −1.282, −1.645, and − 1.96. We used Chi-square tests and Cohen’s kappa statistics to evaluate the relationship between SRB change and presence/absence of subjective cognitive decline at follow-up. We also examined the prevalence rates of different symptom combinations in an amyloid positive sample (n = 29). Results The base rate of having at least one significant SRB decline ranged from 26.00% to 59.40%. Subjective cognitive decline was positively associated with SRB-defined decline in the normative sample, though agreement was limited (= − .01–.10). SRB decline with no subjective decline occurred in 0.0–37.90% of amyloid positive participants, while 3.40–37.90% had subjective but not objective decline. 37.90–79.30% of amyloid positive participants exhibited either SRB or subjective decline. Conclusions Subjective and objective cognitive declines appear to represent unique symptom classes and should be separately considered when staging patients on the Alzheimer’s Continuum.

Influence of the age factor on pre-mild cognitive impairment

Pre-Mild Cognitive Impairment (PreMCI) is characterized by patients’ complaints of memory impairment and/or other cognitive functions. In elderly and senile age, PreMCI can be a predictor of the development of more significant cognitive defects up to the development of dementia. The study was aimed at the analysis of the neuropsychological characteristics of patients with PreMCI in dependence on their age. Materials and methods . The results of the examination of 547 patients (159 men and 388 women) in the age groups of 45–59 years old, 60–74 years old and 75–89 years old were analyzed in comparison to 104 healthy subjects with the same age characteristics who did not complain of cognitive functions’ impairment. The study included clinical research and the use of scales and questionnaires set evaluating cognitive functions. Results . Significant differences were detected between patients with PreMCI and healthy subjects of middle and old age in most neuropsychological tests. Patients over 75 years old differed from healthy ones only in the clock drawing test and immediate reproduction of 12 words test. Most significant difference in neuropsychological tests in different age groups of healthy subjects was impairment in executive functions and the index of the 12-word immediate reproduction test. Patients with PreMCI had a deterioration of divided-attention measure indicators, executive and language functions, and constructional praxis, while in memory tests no significant dynamics was detected. Conclusion . A broader spectrum of cognitive functions’ defects is detected in patients with PreMCI compared to healthy ones. At the same time, memory impairment is a fixed condition, and is not essentially dependent on age.

Visual Object Discrimination Impairment as an Early Predictor of Mild Cognitive Impairment and Alzheimer's Disease.

Detection of cognitive impairment suggestive of risk for Alzheimer's disease (AD) progression is crucial to the prevention of incipient dementia. This study was performed to determine if performance on a novel object discrimination task improved identification of earlier deficits in older adults at risk for AD. In total, 135 participants from the 1Florida Alzheimer's Disease Research Center [cognitively normal (CN), Pre-mild cognitive impairment (PreMCI), amnestic mild cognitive impairment (aMCI), and dementia] completed a test of object discrimination and traditional memory measures in the context of a larger neuropsychological and clinical evaluation. The Object Recognition and Discrimination Task (ORDT) revealed significant differences between the PreMCI, aMCI, and dementia groups versus CN individuals. Moreover, relative risk of being classified as PreMCI rather than CN increased as an inverse function of ORDT score. Overall, the obtained results suggest that a novel object discrimination task improves the detection of very early AD-related cognitive impairment, increasing the window for therapeutic intervention. (JINS, 2019, 25, 688-698).

Classification of Neurodegenerative Disease Stages using Ensemble Machine Learning Classifiers

Existing research works for Alzheimer’s disease (AD) can predict the prevalence of disease only after the advancement of the disease. With these existing prediction models, it is possible only to reduce and delay the symptoms of the disease. The exact usefulness is when the presence of the disease is identified at an early stage and this early detection makes a great impact in subjects’ recovery. Thus, early detection of controls at high risk of development of Alzheimer’s disease is of a key objective of the proposed work. Existing machine learning and deep learning algorithms derive only limited predictive accuracy. Also, they derive results based on expensive machine learning algorithms that had hard-to-collect features and classifying becomes complex with numerous overfitting in choosing decision boundaries. The proposed study intends to develop a learning algorithm for the prediction of Alzheimer’s disease at an early stage. It also classifies the features if the subjects with Mild Cognitive impairment (MCI) and Pre-Mild Cognitive Impairment (Pre-MCI)has the likelihood to develop Alzheimer’s disease. A dataset of AD controls was used to train different machine learning algorithms. Onset information like social behavior, demographic characteristics, neurological test scores, clinical cardiovascular index, and brain atrophy ratio can also be used as the extract predictor. A validation procedure was applied to identify a relevant subset of predictors. The conversion to AD in MCI and Pre MCI subjects are based only on non-invasively and effectively collectible predictors.

A clinically-translatable machine learning algorithm for the prediction of Alzheimer's disease conversion: further evidence of its accuracy via a transfer learning approach.

In a previous study, we developed a highly performant and clinically-translatable machine learning algorithm for a prediction of three-year conversion to Alzheimer's disease (AD) in subjects with Mild Cognitive Impairment (MCI) and Pre-mild Cognitive Impairment. Further tests are necessary to demonstrate its accuracy when applied to subjects not used in the original training process. In this study, we aimed to provide preliminary evidence of this via a transfer learning approach. We initially employed the same baseline information (i.e. clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy) and the same machine learning technique (support vector machine with radial-basis function kernel) used in our previous study to retrain the algorithm to discriminate between participants with AD (n = 75) and normal cognition (n = 197). Then, the algorithm was applied to perform the original task of predicting the three-year conversion to AD in the sample of 61 MCI subjects that we used in the previous study. Even after the retraining, the algorithm demonstrated a significant predictive performance in the MCI sample (AUC = 0.821, 95% CI bootstrap = 0.705-0.912, best balanced accuracy = 0.779, sensitivity = 0.852, specificity = 0.706). These results provide a first indirect evidence that our original algorithm can also perform relevant generalized predictions when applied to new MCI individuals. This motivates future efforts to bring the algorithm to sufficient levels of optimization and trustworthiness that will allow its application in both clinical and research settings.

Effects of Transcranial Direct Current Stimulation on Episodic Memory in Amnestic Mild Cognitive Impairment: A Pilot Study.

Episodic memory is impaired in amnestic mild cognitive impairment (aMCI), which is posited as a potential prodromal form of Alzheimer's disease. Reactivated existing memories become sensitive to modification during reconsolidation. There is evidence that the lateral prefrontal cortex (PFC) plays causal role in episodic memory reconsolidation. Transcranial direct current stimulation (tDCS) applied to the PFC after a contextual reminder enhanced episodic memory performance up to 1 month, conceivably through reconsolidation, in older adults with subjective memory complaints, a condition that may represent a "pre-mild cognitive impairment" stage. The aim of this pilot study was to test the effect of PFC-tDCS (anode over left lateral PFC, cathode over right supraorbital area) after a contextual reminder on episodic memory in older adults with aMCI. Older adults with aMCI learned a list of words. Twenty-four hours later, tDCS (Active or Sham) was applied after a contextual reminder. Memory retrieval (free recall and recognition) was tested 48 hrs and 1 month after the learning session. Active tDCS enhanced recognition memory relative to Sham stimulation. Modulating reconsolidation with PFC-tDCS might be a novel intervention to enhance episodic memories in aMCI.

Pre-Mild Cognitive Impairment: Can Visual Memory Predict Who Rapidly Convert to Mild Cognitive Impairment?

ObjectiveLittle is known about the natural course of pre-mild cognitive impairment (pre-MCI) and predictors to MCI. We followed-up individuals with pre-MCI and cognitively normal (CN) elders to identify neuropsychological predictors for rapid conversion to MCI. MethodsSeventy-seven individuals with pre-MCI and 180 CN elders were recruited from the pool of individuals registered at the National Research Center for Dementia in Gwangju, Korea. We followed-up with them after a mean of 14±2.29 months. All participants underwent comprehensive clinical and neuropsychological assessment. Logistic regression analysis examined the ability of neuropsychological tests to predict conversions to MCI. ResultsOf 257 participants, 142 (55.3%) were eligible for the follow-up study (102 CN, 40 pre-MCI). Logistic regression revealed that spatial delayed recall significantly predicted the conversion from pre-MCI to MCI. In CN, copy for a complex figure significantly predicted the conversion to pre-MCI or MCI. ConclusionOur findings indicated that spatial delayed recall was associated with rapid conversion from pre-MCI to MCI. Spatial organization and planning, measured by complex figure reproduction, were associated with rapid conversion from CN to pre-MCI or MCI. Our study suggests that inclusion of visuospatial reproduction and memory using a complex figure further facilitates early detection of MCI.